2003 Fiscal Year Final Research Report Summary

Prediction and control of base sequence recognition ability for nucleic acid binding proteins by using computer experiments.

Research Project

Project/Area Number	14598001
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	ポストゲノムのナノサイエンス
Research Institution	Hirosaki University
Principal Investigator	SAITO Minoru Hirosaki University, Faculty of Science and Technology, Professor, 理工学部, 教授 (60196011)
Project Period (FY)	2002 – 2003
Keywords	computer experiment / DNA binding protein / binding affinity / free energy calculation / MD simulation / molecular substitution
Research Abstract	The purpose of this study was to calculate binding affinity between a DNA binding protein and a DNA by expanding my methodology(computational mutation→MD simulation→free energy calculation) which was developed to calculate unfolding free energy differences between a wild type protein and mutant proteins. Another purpose is to clarify the molecular mechanism of the base sequence recognition by DNA binding proteins using the developed method. To complete the purpose, I made it possible to substitute a DNA base to other bases for the simple case, i.e., thymine→uracil substitution. We calculated the binding free energy change due to the thymine→uracil substitution for the DNA-λ-repressor complex. The calculated value(1.5kcal/mol) was in good agreement with the respective experimental value(1.8kcal/mol). We clarified how the λ-repressor recognizes such small difference between thymine→uracil on the atomic level details.